P-TEFb et Brd4

Abstract

Most cell physiology events are dictated by the integration of perceived signals and the elaboration by cells of adapted answers via the execution of proper transcriptional programs. In order to ensure an optimal control of these answers, many regulation mechanisms have been selected throughout the evolution, thus allowing to fine-tune transcript expression. The transcriptional pause and its release by P-TEFb (Positive Transcription Elongation Factor) have been evidenced two decades ago. Since then, the importance of such mechanisms has been highlighted by the association between alterations of this machinery and the appearance of diseases. P-TEFb and Brd4 have thus recently emerged as potential therapeutical targets for cancers and AIDS notably. In this review, we present a brief case history and an up-to-date synthesis of models for transcriptional pause release. We later discuss on the pathophysiological processes associated with this mechanism and clinical trials targeting Brd4 and P-TEFb.

Novel BRD4-p53 Inhibitor SDU-071 Suppresses Proliferation and Migration of MDA-MB-231 Triple-Negative Breast Cancer Cells

“…2 Positive transcription elongation factor b (P-TEFb), which is a Pol II pauserelease factor, is often recruited by BRD4 in stress responses to regulate a wide range of physiological processes and diseases. 3 BRD4 dysfunction has been associated with the onset and progression of numerous human diseases, including cancer, 4 cardiovascular diseases, 5 inflammation, 6 neurological disorders, 7 and obesity. 8 Targeted inhibition of BRD4 triggers apoptosis and inhibits cancer growth, as seen in acute myeloid leukemia, 9 large B cell lymphoma, 10 prostate cancer, 11 pancreatic cancer, 12 ovarian carcinoma, 13 glioma 14 and triplenegative breast cancer (TNBC).…”